Pharmacological basis for treatment of GI disorders Flashcards
Give some H2 Receptor Antagonists.
Cimetidine
Ranitidine
Famotidine
Nizatidine
How do H2 receptor antagonists work?
Inhibit histamine, Ach and gastrin stimulated acid secretion from parietal cells by blocking H2 receptor
also promote healing of duodenal ulcers, but stopping treatment causes relapse
Which H2-receptor antagonist can cause gynecomastia?
Cimetidine
Which H2 antagonist inhibits P450 enzymes?
Cimetidine inhibits P450 enzymes, decreasing number of drugs metabolised by these enzymes.
Give someProton Pump Inhibitors (PPIs).
Omeprazole, Lanzoprazole, Pantoprazole, Rabeprazole
How do PPIs work?
Irreversible inhibit the H+/K+ ATPase in parietal cells, inhibiting gastric acid secretion
What is the function of PGE2 and PGI2?
gastro protective
inhibit gastric acid secretion and stimulate mucus and bicarbonate secretion, providing protection
What is the function of Misoprolol?
stable analogue of PGE1
- inhibits gastric acid secretion
- inhibits activity of parietal cells
- increases mucosal blood flow and can increase secretion of bicarbonate and mucus
What is thCaution of misoprolol?
induces labour and abortion
What is the effect of Dopamine on gut motility and emptying?
Relaxes gut by activating D2 receptors in LOS and stomach (fundus and antrum)
also inhibits release of Ach from myenteric neurones, preventing contraction of gut smooth muscle (inhibits gastric motility and emptying)
Give an example of a D2 Receptor Antagonist.
Metoclopramide
What is the effect of Metoclopramide on gastric motility and emptying?
Increases gastric motility by inhibiting presynaptic and postsynaptic D2 receptors and inhibits 5-HT3 receptors in CNS, increasing gastric motility and also acting as an antiemetic
prokinetic effects are stimulating 5-HT4 receptors in ENS, increasing Ach release from myenteric neurones, increasing LOS and gastric tone, increasing intragastric pressure and accelerating emptying (relaxes pyloric sphincter)
also stimulates inhibitory nitrenergic neurones mediating NO release
*all reduces likelihood of reflux
Give some examples of Anti-spasmodic agents.
propantheline
diclocxerine (dycyclomine)
mebeverine
How do anti-spasmodic drugs work?
Reduce muscle spasms in the bowel and relax smooth muscle in the GIT
useful in IBS and diverticular diseases
What is the role of Muscarinic receptor antagonists during spasms?
Inhibit parasympathetic activity, reducing spasms in the bowel
What is the function of Pharmacological Intervention in gastric ulcer?
- Reduce acid secretion with H2 receptor antagonists
- Neutralise secreted acid with antacids
- Attempt to eradicate H.pylori
What is the function of Antacids?
Neutralise gastric acid and increase pH
form a raft on top of acidic chyme which reduces amount of acidic chyme that refluxes into and damages oesophagus
What is the role of Bismuth chelate?
Absorbs pepsin (stops it from working) and increases HCO3- and PG secretion, protecting the gastric mucosa
also is toxic against H.pylori
What is the Bismuth chelate effect on stool and tongue?
Blackens stool and tongue
What is the Caution of bismuth chelate?
If patient has renal impairment, concentration of bismuth chelate in blood will rise and can cause encephalopathy
Why do NSAIDs (e.g. aspirin) cause gastric bleeding?
Because they inhibit PG synthesis (less protection) and Thromboxane A2 (involved in healing)
COX-2 inhibitors are more stomach friendly and cause less bleeding (e.g. Celecoxib and Rofecoxib)
Describe Combination therapy against H.pylori.
- Omeprazole, amoxicillin, metronidazole
- Omeprazole, clarythromycin and amoxicillin or tetracycline, metronidazole and bismuth chelates
- Lansoprazole, clarithromycin, tinidazole and bismuth chelates
They also cannot drink alcohol if they take metronidazole as it results in disulfiram like reaction, the patient will feel severely ill and may stop taking the drug.
-> Disulfiram inhibits aldehyde dehydrogenase causing a build-up of acetaldehyde, resulting in unpleasant flushing and nausea.
Also, do not give in the first trimester as it will affect the foetus and cause birth defects
What is Constipation?
Increased water loss from faeces leading to drier faeces, making it more painful and harder to defecate
Give some Causes of constipation.
Decreased motility of large intestine due to:
- old age
- damage to ENS
Give some Factors that increase colonic motility.
Increased fibre, cellulose and complex polysaccharides
Laxatives (but excessive use will decrease responsiveness to them)
Mineral oil (lubricates faeces)
Castor oil (stimulates motility of colon)
Name some Drugs to manage constipation.
Purgatives
Bulk forming laxatives
Osmotic laxatives (lactulose)
What is Diarrhoea?
Frequent passage of liquid faeces
What is Loperamide and Codeine?
Antidiarrhoeal agent which decreases intestinal motility and decreases passage of faeces and decreases duration of illness
What is the function of bismuth subsalicylate (chelate)?
Decreases fluid secretion in bowel
How does loperamide work?
u-opioid receptor agonist of the myenteric plexus of large intestine
reduces smooth muscle activity in the GIT, reducing force of colonic movement and thus reduces passage of faeces
increases haustral mixing of proximal colon and inhibits propulsive mass movement of the distal colon
does not cross blood brain barrier therefore has no CNS effects
inhibits gastric emptying, increases sphincter tone, induces stationary motor patterns and blocks peristalsis
